The solution structure of BMPR-IA reveals a local disorder-to-order transition upon BMP-2 binding.
The structure of the extracellular domain of BMP receptor IA was determined in solution by NMR spectroscopy and compared to its structure when bound to its ligand BMP-2. While most parts of the secondary structure are highly conserved between the bound and unbound forms, large conformational rearrangements can be observed in the beta4beta5 loop of BMPR-IA, which is in contact with BMP-2 and harbors the main binding determinants for the BMPR-IA-BMP-2 interaction. In its unbound form, helix alpha1 in BMPR-IA, which is in the center of the binding epitope for BMP-2, is missing. Since BMP-2 also shows conformational changes in the type I receptor epitope upon binding to BMPR-IA, both binding partners pass through an induced fit mechanism to adapt their binding interfaces to a given interaction surface. The inherent flexibility of both partners possibly explains the promiscuous ligand-receptor interaction observed in the BMP protein superfamily.
Klages
Jochen
J
Center of Integrated Protein Science (CIPSM) at the Technische Universitat Munchen, Lichtenbergstrasse 4, D-85747 Garching, Germany.
Kotzsch
Alexander
A
Coles
Murray
M
Sebald
Walter
W
Nickel
Joachim
J
Müller
Thomas
T
Kessler
Horst
H
D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I